1xuz | pdb_00001xuz

Crystal structure analysis of sialic acid synthase (NeuB)from Neisseria meningitidis, bound to Mn2+, Phosphoenolpyruvate, and N-acetyl mannosaminitol

spinqualitylabelsall models 1xuz, resolution 2.20Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 1xuz is a 1 chain structure with sequence from "diplokokkus_intracellularis_meningitidis"_(sic)_weichselbaum_1887 "diplokokkus intracellularis meningitidis" (sic) weichselbaum 1887. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: MMN, MN, PEP Related: 1xuu Gene: neuB ("Diplokokkus intracellularis meningitidis" (sic) Weichselbaum 1887) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed In Neisseria meningitidis and related bacterial pathogens, sialic acids play critical roles in mammalian cell immunity evasion and are synthesized by a conserved enzymatic pathway that includes sialic acid synthase (NeuB, SiaC, or SynC). NeuB catalyzes the condensation of phosphoenolpyruvate (PEP) and N-acetylmannosamine, directly forming N-acetylneuraminic acid (or sialic acid). In this paper we report the development of a coupled assay to monitor NeuB reaction kinetics and an 18O-labeling study that demonstrates the synthase operates via a C-O bond cleavage mechanism. We also report the first structure of a sialic acid synthase, that of NeuB, revealing a unique domain-swapped homodimer architecture consisting of a (beta/alpha)8 barrel (TIM barrel)-type fold at the N-terminal end and a domain with high sequence identity and structural similarity to the ice binding type III antifreeze proteins at the C-terminal end of the enzyme. We have determined the structures of NeuB in the malate-bound form and with bound PEP and the substrate analog N-acetylmannosaminitol to 1.9 and 2.2 A resolution, respectively. Typical of other TIM barrel proteins, the active site of NeuB is located in a cavity at the C-terminal end of the barrel; however, the positioning of the swapped antifreeze-like domain from the adjacent monomer provides key residues for hydrogen bonding with substrates in the active site of NeuB, a structural feature that leads to distinct modes of substrate binding from other PEP-utilizing enzymes that lack an analogous antifreeze-like domain. Our observation of a direct interaction between a highly ordered manganese and the N-acetylmannosaminitol in the NeuB active site also suggests an essential role for the ion as an electrophilic catalyst that activates the N-acetylmannosamine carbonyl to the addition of PEP. Structural and mechanistic analysis of sialic acid synthase NeuB from Neisseria meningitidis in complex with Mn2+, phosphoenolpyruvate, and N-acetylmannosaminitol.,Gunawan J, Simard D, Gilbert M, Lovering AL, Wakarchuk WW, Tanner ME, Strynadka NC J Biol Chem. 2005 Feb 4;280(5):3555-63. Epub 2004 Oct 29. PMID:15516336 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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